Numerous experiments in our laboratory have shown that exposure to an acute stressful experience facilitates associative learning in male rats and dramatically impairs learning in female rats. We have also found sex differences and opposing effects of stress on dendritic spine density in the hippocampus of males versus females. In males, spine density is enhanced after exposure to an acute stressor, while the density of dendritic spines in females is reduced. Based on this series of observations, we have proposed that the stress effects on learning are mediated by the stress effects on spine density. To address this hypothesis, I will test whether the opposite effects of stress on earning in males versus females. In males, the stress-induced facilitation of learning is dependent on the stress-related adrenal hormones, glucocorticoids. The stress-induced impairment of learning in females is not dependent on the stress-related glucocorticoids, but is dependent on the ovarian hormone estrogen. Thus, the goal of my proposal is to determine whether glucocorticoids in males and estrogen in females contribute to the sexually opposed stress on dendritic spine density.